Determinanten der Anfälligkeit Frühgeborener für bakterielle Infektionen: Untersuchungen zur angeborenen Immunität gegenüber Koagulase-negativen Staphylokokken
Final Report Abstract
Preterm infants account for ~75% of neonatal morbidity and mortality and result in significant health care cost. Preterm infants are uniquely susceptible to infection and this results in much of the mortality and morbidity both directly and indirectly by driving pathological inflammation. In this project we aimed to characterize how the innate host response of preterm infants to the most common bacterial pathogen, Staphylococcus epidermidis (SE), differs from that of older infants and adults. We first characterized the immunological properties of the bacterial preparations and found that inactivation of bacteria has significant qualitative and quantitative effects on how they interact with the human innate immune system. We therefore suggest that any interpretation of in vitro data need take into account the potential effects of bacterial inactivation and we should not assume that responses to killed organisms are necessarily similar to those of live bacteria. Future studies should include live bacteria in addition to inactivated preparations. Our investigations into the interaction of SE with the human immune system demonstrate the importance of Toll-like receptor 2 in recognition of whole, live SE in vitro and to clearance of SE bacteremia in vivo. In this context, our study may have clinical implications for defining mechanisms of susceptibility in SE-susceptible populations and for developing novel adjunctive approaches to prevent and/or treat SE infection. When specifically examining the ability of preterm infants’ cells to react to the two most common pathogens SE and Group B streptococci, we found that some these responses are severely impaired in the most immature infants. This significantly adds to our understanding of the susceptibility of preterm infants to serious infections. We are currently conducting further studies that aim to delineate the underlying deficiency and to find tests that allow for early detection of those babies at highest risk for infection.
Publications
- Reduced levels of antimicrobial proteins and peptides in human cord blood plasma. (Arch Dis Child, Fetal & Neonatal edition 2009; 94:230-31)
Strunk T, Doherty D, Richmond P, Simmer K, Charles A, Levy O, Liyanage K, Smith T, Currie A, Burgner D
